High Dose of Liraglutide Impairs Renal Function in Female Hypertensive Rats

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known for cardiovascular benefits.
• The specific renal effects of varying liraglutide doses in essential hypertension models remain under-investigated.

Purpose of the Study:

• To investigate the dose-dependent renal effects of liraglutide in female spontaneously hypertensive rats.

Main Methods:

• Rats received saline, low-dose (0.06 mg/kg), or high-dose (0.6 mg/kg) liraglutide twice daily for 30 days.
• Renal function markers, including volume excretion, urine/serum urea and creatinine ratios, and tissue analyses (nitrite, nitrate, oxidation products, collagen), were assessed.
• Effects were evaluated independently of blood pressure and glycemic control.

Main Results:

• Liraglutide reduced body weight gain in both dose groups.
• High-dose liraglutide increased urinary volume excretion and the sodium/potassium ratio.
• High-dose liraglutide elevated markers of kidney injury (urea, urea/creatinine ratio), increased collagen deposition, altered renal nitrite/nitrate balance, and aberrantly increased glomerular filtration rate.
• Low-dose liraglutide reduced advanced protein oxidation products and urinary urea/creatinine ratio.

Conclusions:

• Liraglutide exhibits distinct, dose-dependent renal effects in a model of essential hypertension.
• Higher doses of liraglutide appear to impair kidney function and exacerbate injury markers, independent of blood pressure or glucose levels.
• Lower doses may offer some renal protective benefits, suggesting a need for careful dose selection in hypertensive patients.